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Abstract Isotopic fractionation has been linked to the lattice vibrations of materials through their phonon spectra. The Lamb-Mössbauer factor (fLM) has the potential to provide information about the lattice vibrations in materials. We constrain the temperature evolution of the fLM of γ- and ε-Fe at in situ high-P-T conditions between 1650 K and the melting point. We find that the vibrations of γ- and ε-Fe can be described using a quasiharmonic model with a pressure- and temperature-dependent Debye temperature computed from the measured fLM. From the Debye temperature, we derive the equilibrium isotopic fractionation β-factor of iron. Our results show that the quasiharmonic behavior of metallic iron would lower the value of lnβFe57/54 by 0.1‰ at 1600–2800 K and 50 GPa when compared to the extrapolation of room temperature nuclear resonant inelastic X-ray scattering data. Our study suggests that anharmonicity may be more prevalent in Fe metal than in lower mantle minerals at 2800 K and 50 GPa, a relevant condition for the core formation, and the silicate mantle may be isotopically heavy in iron. 

Abstract Single crystals of Al-free, ferromagnesian jeffbenite up to 200 µm in size have been synthesized at 15 GPa and 1200 °C in a 1200 tonne multi-anvil press from a starting composition in the forsteritefayalite-magnetite-water system. This phase has the approximate formula Mg2.62Fe0.872+Fe1.633+Si2.88O12 and is observed to coexist with a Ca-free clinopyroxene plus what appears to be quenched melt. The crystal structure has been refined from single-crystal X-ray diffraction data and is similar to that determined for natural Al-bearing jeffbenite, Mg3Al2Si3O12, reported from inclusions in superdeep diamonds. The structure is a tetragonal orthosilicate in space group I42d with a = 6.6449(4) Å, c = 18.4823(14) Å, and is structurally more closely related to zircon than to garnet. The T2 site is larger than T1, shares an edge with the M2 octahedron, and incorporates significant Fe3+. Because of the tetrahedral incorporation of trivalent cations, jeffbenite appears to be compositionally distinct from garnet. Previous speculations that the phase may only occur as a retrograde decompression product from bridgmanite are not supported by its direct synthesis under transition zone conditions. The phase has a calculated density of 3.93 g/cm3, which is indistinguishable from a garnet of comparable composition, and is a possible component in the mantle transition zone under oxidizing conditions or with Al-rich compositions. 

The transcriptional co-activator YAP1 (yes-associated protein 1) is a critical nuclear effector of the Hippo pathway. The Hippo pathway regulates cell growth, cell motility, cell migration, and carcinogenesis, but poorly defined mechanism. We investigated biochemical and functional interactions between YAP1 and the nuclear factor (NF)-kappa B/RELA subunit in prostate cancer cell models. We demonstrated that endogenous YAP1 and RELA form protein complexes in the cell, as revealed by co-immunoprecipitation and western blotting. Compared with control, we found that combined treatment of cells with androgen and SDF-1a (stromal cell-derived factor-1 alpha) or RANKL (receptor activator of NF-kappa B ligand) enhanced the protein-protein interaction between YAP1 and RELA, as showed by proximity ligation assay. Our confocal microscopy experiment further showed that combined SDF-1aand androgen treatment promoted the YAP1 and RELA colocalization instead of single-agent treatment. Moreover, our promoter-reporter and RNAi experiments showed that knockdown of YAP1 or TEAD, a key mediator of the YAP transcription, significantly reduced the NF-Kappa B promoter-reporter gene activity. Also, disruption of YAP1 activity attenuated the TEAD-RELA interaction. Furthermore, the controlled expression of MST1/STK4, a potent inhibitor of YAP1, attenuated the NF-Kappa B-promoter reporter activity. Additionally, our unbiased bioinformatics analysis of the exiting ChIP-seq (chromatin immunoprecipitation-sequencing) data sets identified several genes that are likely co-regulated by the YAP1/TEAD and NF-Kappa B/RELA transcription factors. These findings suggest that cooperative androgen and cytokine signaling regulates Hippo/YAP and NF-Kappa B interaction. Thus, the YAP1/TEAD and NF-Kappa B/RELA interaction may have critical roles in cellular biology and human diseases. 

Cell-cell interaction is critical for tissue development and repair, immunological responses, and cancer cell metastasis. The tyrosine kinase EPHA3 (erythropoietin‑producing hepatocellular carcinoma cell surface type-A receptor 3) regulates cell-cell interaction, cell differentiation, and cancer cell survival. Previously, our published study indicated that the theSTK4-encoded MST1 signaling, a core kinase component of the Hippo pathway, suppressedEPHA3 expression in the prostate cancer cell models. However, the mechanism is unknown. Here, we have demonstrated that the YAP1 and TEAD1 proteins, critical nuclear effectors of the Hippo pathway, mediate EPHA3 expression. First, we showed that AR-positive cell lines express the highest levels of EPHA3 and its ligand, ephrin-A5, transcripts compared with other EPH family members. Second, we demonstrated the induction of MST1/STK4attenuated the EPHA3 protein and transcripts, consistent with our initial observation. Next, we demonstrated that the knockdown of YAP1 by siRNA suppressed EPHA3 protein and mRNA expression. Similarly, the silencing of the TEAD1-4 proteins, critical mediators of YAP1-dependent gene transcription, revealed that the TEAD1 is a crucial inducer of EPHA3expression. Moreover, bioinformatics tools allowed the identification of three putative TEAD binding sites (p<0.001) in the promoter region of the EPHA3 gene. Furthermore, CRISPR/Cas9-aided EPHA3 knockout significantly (p<0.01), decreased cell growth in monolayer and sphere formation in 3D cultures, and caused androgen-independent cells to become sensitive to enzalutamide, a potent direct inhibitor of AR activity. These observations suggest that the YAP/TEAD1 transcriptionally regulates EPHA3 and its cellular biology. 

Abstract Electronic states of iron in the lower mantle's dominant mineral, (Mg,Fe,Al)(Fe,Al,Si)O3 bridgmanite, control physical properties of the mantle including density, elasticity, and electrical and thermal conductivity. However, the determination of electronic states of iron has been controversial, in part due to different interpretations of Mössbauer spectroscopy results used to identify spin state, valence state, and site occupancy of iron. We applied energy-domain Mössbauer spectroscopy to a set of four bridgmanite samples spanning a wide range of compositions: 10–50% Fe/total cations, 0–25% Al/total cations, 12–100% Fe3+/total Fe. Measurements performed in the diamond-anvil cell at pressures up to 76 GPa below and above the high to low spin transition in Fe3+ provide a Mössbauer reference library for bridgmanite and demonstrate the effects of pressure and composition on electronic states of iron. Results indicate that although the spin transition in Fe3+ in the bridgmanite B-site occurs as predicted, it does not strongly affect the observed quadrupole splitting of 1.4 mm/s, and only decreases center shift for this site to 0 mm/s at ~70 GPa. Thus center shift can easily distinguish Fe3+ from Fe2+ at high pressure, which exhibits two distinct Mössbauer sites with center shift ~1 mm/s and quadrupole splitting 2.4–3.1 and 3.9 mm/s at ~70 GPa. Correct quantification of Fe3+/total Fe in bridgmanite is required to constrain the effects of composition and redox states in experimental measurements of seismic properties of bridgmanite. In Fe-rich, mixed-valence bridgmanite at deep-mantle-relevant pressures, up to ~20% of the Fe may be a Fe2.5+ charge transfer component, which should enhance electrical and thermal conductivity in Fe-rich heterogeneities at the base of Earth's mantle.